Enzyme-Responsive PEG-Dendron Hybrids as a Platform for Smart Nanocarriers

Disease-associated enzymes are highly promising stimuli for the enzyme-responsive disassembly of smart micellar carriers of drugs and imaging probes. Together with this great potential, the use of enzymes raises many challenges compared to other types of stimuli such as pH, temperature, or light. Unlike these nearly dimensionless' stimuli, an enzyme, which can be of an approximately similar size as the carrier, must reach the enzyme-sensitive moieties that are spread along the backbone of the polymer and might be hidden inside the hydrophobic cores of the self-assembled structures. Recent publications demonstrate the utilization of well-defined dendron-based hybrids as highly modular tools to study the molecular mechanisms of enzymatically induced disassembly. A simple polyethylene glycol-dendron hybrid bearing hydrophobic enzymatically cleavable end-groups allowed us to address key questions in this field. Using this system, we obtained high molecular resolution of the enzymatically induced disassembly process and were able to evaluate whether the enzyme penetrates through the micelle's shell into its core, or interacts with the polymers in their monomeric form only, which is in equilibrium with the assembled state. The kinetic studies clearly indicate an equilibrium-based mechanism that fits very well with kinetic data for other enzyme-responsive polymeric amphiphiles.